Diabetes mellitus by dr shahjada selim

Diabetes Mellitus
Dr Shahjada Selim
Endocrinologist
Shaheed Suhrawardy Medical College
Hospital, Dhaka
Email: selimshahjada@gmail.com

Diabetes Mellitus
Diabetes is a chronic state of hyperglycemia
due to deficiency of insulin secretion, its action
or both.

Diabetes is a huge and growing problem, and
the costs to society are high and escalating
382 million people have
diabetes
By 2035, this number will
rise to 592 million

Diabetes is a huge and growing problem, and
the costs to society are high and escalating
Globally
382 million people have
diabetes
By 2035, this number will rise
to 592 million
In Bangladesh
8.4 million people had diabetes
in 2013
8.4 million people are likely to
have diabetes in 2035

Almost half of all
people with
diabetes live in
just three
countries
• China
• India
• USA

Increasing
development
and
wealth is
correlated
with
decreasing
early
mortality
due to
diabetes

What goes wrong in diabetes?
 Multitude of mechanisms
Insulin
 Regulation
 Secretion
 Uptake or breakdown
Beta cells
 Damage

Action of Insulin on Carbohydrate,
Protein and Fat Metabolism
Carbohydrate
 Facilitates the transport of glucose into
muscle and adipose cells
 Facilitates the conversion of glucose to
glycogen for storage in the liver and
muscle.
 Decreases the breakdown and release of
glucose from glycogen by the liver

Protein
 Stimulates protein synthesis
 Inhibits protein breakdown; diminishes
gluconeogenesis

Fat
 Stimulates lipogenesis- the transport of
triglycerides to adipose tissue
 Inhibits lipolysis – prevents excessive
production of ketones or ketoacidosis

19
Classification of DM
1. Type 1 DM
 It is due to insulin deficiency and is formerly known as.
 Type I
 Insulin Dependent DM (IDDM)
 Juvenile onset DM
2. Type 2 DM
 It is a combined insulin resistance and relative deficiency in
insulin secretion and is frequently known as.
 Type II
 Noninsulin Dependent DM (NIDDM)
 Adult onset DM

20
3. Gestational Diabetes Mellitus (GDM):
 Gestational Diabetes Mellitus (GDM) developing during some
cases of pregnancy but usually disappears after pregnancy.
4. Other types:
 Secondary DM

21
Etiology
1. Etiology of Type 1 Diabetes

23
2. Etiology of Type 2 Diabetes

25
Risk Factors
 Type 1 DM

Genetic predisposition
In an individual with a genetic
predisposition, an event such as virus
or toxin triggers autoimmune
destruction of β-cells probably over a
period of several years.

26
Risk Factors
 Type 2 DM
 Family History
 Obesity
 Habitual physical inactivity
 Previously identified impaired glucose tolerance
(IGT) or impaired fasting glucose (IFG)
 Hypertension
 Hyperlipidemia

27
Diagnostic Criteria
• Any one test should be confirmed with a second test,
most often fasting plasma glucose (FPG).
• This criteria for diagnosis should be confirmed by
repeating the test on a different day.

30
Clinical Presentation
 Type 1 DM
- Polyuria
- Polydipsia
- Polyphagia
- Weight loss
- Weakness
- Dry skin
- Ketoacidosis
• Type 2 DM
- Patients can be asymptomatic
- Polyuria
- Polydipsia
- Polyphagia
- Fatigue
- Weight loss
- Most patients are discovered
while performing urine glucose
screening

Management of
Diabetes Mellitus

The major components of the treatment of diabetes are:
Management of DM

 Diet is a basic part of management in every
case. Treatment cannot be effective unless
adequate attention is given to ensuring
appropriate nutrition.
A. Diet

Dietary treatment should aim at:
◦ ensuring weight control
◦ providing nutritional requirements
◦ allowing good glycaemic control with
blood glucose levels as close to normal as
possible
◦ correcting any associated blood lipid
abnormalities
A. Diet

The following principles are recommended as
dietary guidelines for people with diabetes:
 Dietary fat should provide 25-35% of total
intake of calories but saturated fat intake
should not exceed 10% of total energy.
Cholesterol consumption should be restricted
and limited to 300 mg or less daily.
A. Diet (cont.)

 Protein intake can range between 10-15%
total energy (0.8-1 g/kg of desirable body
weight). Requirements increase for children
and during pregnancy. Protein should be
derived from both animal and vegetable
sources.
A. Diet (cont.)

The following principles are recommended as
dietary guidelines for people with diabetes:
 Carbohydrates provide 50-60% of total caloric
content of the diet. Carbohydrates should be
complex and high in fibre.
 Excessive salt intake is to be avoided. It should
be particularly restricted in people with
hypertension and those with nephropathy.
A. Diet (cont.)

 Physical activity promotes weight
reduction and improves insulin
sensitivity, thus lowering blood glucose
levels.
Exercise

 Together with dietary treatment, a
programme of regular physical activity and
exercise should be considered for each
person. Such a programme must be tailored
to the individual’s health status and fitness.
 People should, however, be educated about
the potential risk of hypoglycaemia and how
to avoid it.
Exercise

 There are currently four classes of oral anti-
diabetic agents:
i. Biguanides
ii. Insulin Secretagogues – Sulphonylureas
iii. Insulin Secretagogues – Non-sulphonylureas
iv. α-glucosidase inhibitors
v. Thiazolidinediones (TZDs)
vi. DPP4i
B. Oral Anti-Diabetic Agents

 If glycaemic control is not achieved (HbA1c > 6.5%
and/or; FPG > 7.0 mmol/L or; RPG >11.0mmol/L) with
lifestyle modification within 1 –3 months, ORAL ANTI-
DIABETIC AGENT should be initiated.
 In the presence of marked hyperglycaemia in newly
diagnosed symptomatic type 2 diabetes (HbA1c > 8%,
FPG > 11.1 mmol/L, or RPG > 14 mmol/L), oral anti-
diabetic agents can be considered at the outset
together with lifestyle modification.
B.1 Oral Agent Monotherapy

As first line therapy:
 Obese type 2 patients, consider use of metformin, acarbose
or TZD.
 Non-obese type 2 patients, consider the use of metformin
or insulin secretagogues
 Metformin is the drug of choice in overweight/obese
patients. TZDs and acarbose are acceptable alternatives in
those who are intolerant to metformin.
 If monotherapy fails, a combination of TZDs, acarbose and
metformin is recommended. If targets are still not
achieved, insulin secretagogues may be added
B.1 Oral Agent Monotherapy (cont.)

Combination oral agents is indicated in:
 Newly diagnosed symptomatic patients
with HbA1c >10
 Patients who are not reaching targets
after 3 months on monotherapy
B.2 Combination Oral Agents

 If targets have not been reached after optimal
dose of combination therapy for 3 months,
consider adding intermediate-acting/long-
acting insulin (BIDS).
 Combination of insulin+ oral anti-diabetic
agents (BIDS) has been shown to improve
glycaemic control in those not achieving
target despite maximal combination oral
anti-diabetic agents.
B.3 Combination Oral Agents and Insulin

 Combining insulin and the following oral anti-
diabetic agents has been shown to be effective in
people with type 2 diabetes:
◦ Biguanide (metformin)
◦ Insulin secretagogues (sulphonylureas)
◦ Insulin sensitizers (TZDs)(the combination of a TZD plus
insulin is not an approved indication)
◦ α-glucosidase inhibitor (acarbose)
 Insulin dose can be increased until target FPG is
achieved.
B.3 Combination Oral Agents and Insulin

 In elderly non-obese patients, short acting insulin
secretagogues can be started but long acting
Sulphonylureas are to be avoided. Renal function
should be monitored.
 Oral anti-diabetic agent s are not recommended for
diabetes in pregnancy
 Oral anti-diabetic agents are usually not the first line
therapy in diabetes diagnosed during stress, such as
infections. Insulin therapy is recommended for both
the above
General Guidelines for Use of Oral Anti-
Diabetic Agent in Diabetes

 Targets for control are applicable for all age
groups. However, in patients with co-morbidities,
targets are individualized
 When indicated, start with a minimal dose of oral
anti-diabetic agent, while reemphasizing diet and
physical activity. An appropriate duration of time
(2-16 weeks depending on agents used) between
increments should be given to allow achievement
of steady state blood glucose control
General Guidelines for Use of Oral Anti-Diabetic
Agent inDiabetes

Short-term use:
 Acute illness, surgery, stress and emergencies
 Pregnancy
 Breast-feeding
 Insulin may be used as initial therapy in type 2
diabetes
 in marked hyperglycaemia
 Severe metabolic decompensation (diabetic
ketoacidosis, hyperosmolar nonketotic coma,
lactic acidosis, severe hypertriglyceridaemia).
C. Insulin Therapy

Long-term use:
 If targets have not been reached after optimal
dose of combination therapy or BIDS,
consider change to multi-dose insulin therapy.
When initiating this,insulin secretagogues
should be stopped and insulin sensitisers e.g.
Metformin or TZDs, can be continued.
C. Insulin Therapy

 The majority of patients will require more than one daily
injection if good glycaemic control is to be achieved.
However, a once-daily injection of an intermediate
acting preparation may be effectively used in some
patients.
 Twice-daily mixtures of short- and intermediate-acting
insulin is a commonly used regimen.
 In some cases, a mixture of short- and intermediate-
acting insulin may be given in the morning. Further
doses of short-acting insulin are given before lunch and
the evening meal and an evening dose of intermediate-
acting insulin is given at bedtime.
Insulin regimens

 Other regimens based on the same principles
may be used.
 A regimen of multiple injections of short-
acting insulin before the main meals, with an
appropriate dose of an intermediate-acting
insulin given at bedtime, may be used,
particularly when strict glycaemic control is
mandatory.
Insulin regimens

 Patients should be educated to practice self-care.
This allows the patient to assume responsibility and
control of his / her own diabetes management. Self-
care should include:
◦ Blood glucose monitoring
◦ Body weight monitoring
◦ Foot-care
◦ Personal hygiene
◦ Healthy lifestyle/diet or physical activity
◦ Identify targets for control
◦ Stopping smoking
Self-Care of Diabetics

55
Pharmacotherapy :Type 1 DM
Monitoring
- Most Type 1 patients require
0.5-1.0 U/kg/d
- The initial regimen should be modified based
on:
- Symptoms
- SMBG
- HbA1C

56
Pharmacotherapy :Type 1 DM
Monitoring

57
Diabetes Mellitus Complications
1. Hypoglycemia
- Cause: Missing meals or excessive exercise or too
much insulin
- Symptoms: Tachycardia, palpitation, sweating,
nausea, and vomiting. Progress to mental confusion,
bizarre behavior and coma
- Treatment: Candy or sugar
IV glucose
Glucagon 1 gm IM
- Identification: MedicAler bracelet

58
2. Diabetes retinopathy
- Microaneurysm
- Hemorrhage
- Exudates
- Retinal edema
- other

59
3. Diabetes nephropathy
- 30-40 % of all type 1 DM patients develop nephropathy
in 20 years
- 15-20 % of type 2 DM patients develop nephropathy
- Manifested as:
- Microalbuminuria
- Progressive diabetic nephropathy leading to end-
stage renal disease

60
Diabetes nephropathy (Cont’d)
- All diabetic patients should be screened annually for
microalbuminurea to detect patients at high risk of
developing progressive diabetic nephropathy
- Tight glycemic control and management of the blood
pressure can significantly decrease the risk of developing
diabetic nephropathy.
- ACE-inhibitors are recommended to decrease the
progression of nephropathy

61
4. Diabetes neuropathy
Autonomic neuropathy:
- Manifested by orthostatic hypotension, diabetic diarrhea,
erectile dysfunction, and difficulty in urination.

62
5. Peripheral vascular disease and foot ulcer
Incidence of gangrene
of the feet in DM is 20
fold higher than control
group due to:
- Ischemia
- Peripheral neuropathy
- Secondary infection

63
Special Patient Population
1. Adolescent Type 2 DM
- Type 2 DM is increasing in adolescent
- Lifestyle modification is essential in these patients
- If lifestyle modification alone is not effective,
metformin the only labeled oral agent for use in
children (10-16 years)

64
Special Patient Population
2. Gestational DM
- Dietary control
- If blood glucose is not controlled by dietary control, insulin
therapy is initiated
- One dose of NPH or NPH + regular insulin (2:1) given
before breakfast. Adjust regimen according to SMBG.
- Sulfonylureas: Effective, but require further studies to
demonstrate safety.

65
Special Situations
3. Diabetic ketoacidosis
- It is a true emergency
- Usually results from omitting insulin in type 1 DM or
increase insulin requirements in other illness (e.g.
infection, trauma) in type 1 DM and type 2 DM
- Signs and symptoms:
- Fatigue, nausea, vomiting, evidence of dehydration,
rapid deep breathing, fruity breath odor, hypotension
and tachycardia

66
Special Situations
Diabetic ketoacidosis (Cont’d)
- Diagnosis
- Hyperglycemia, acidosis, low serum
bicarbonate, and positive serum ketones
- Abnormalities:
- Dehydration, acidosis, sodium and
potassium deficit
- Patient education is important

67
Special Situations
Diabetic ketoacidosis (Cont’d)
Management:
- Fluid administration: Rapid fluid administration to restore
the vascular volume,
- IV infusion of insulin to restore the metabolic
abnormalities. Titrate the dose according to the blood
glucose level.
- Potassium and phosphate can be added to the fluid if
needed.
Follow up:
- Metabolic improvement is manifested by an
increase in serum bicarbonate or pH.

 Researches have found that lifestyle changes
can prevent or delay the onset of type 2
diabetes among high-risk adults.
 These studies included people with IGT and
other high-risk characteristics for developing
diabetes.
Prevention or delay of diabetes:
Life style modification

 Lifestyle interventions included diet and
moderate-intensity physical activity (such as
walking for 150 mins each week).
 In the Diabetes Prevention Program, a large
prevention study of people at high risk for
diabetes, the development of diabetes was
reduced 58% over 3 years.
Life style modification

 Studies have shown that medications have
been successful in preventing diabetes in
some population groups.
 In the Diabetes Prevention Program, people
treated with the drug metformin reduced
their risk of developing diabetes by 31% over
3 years.
Medications

 Treatment with metformin was most
effective among younger, heavier people
(those 25-40 years of age who were 50 to 80
pounds overweight) and less effective among
older people and people who were not as
overweight. se tolerance.
Medications

 Similarly, in the STOP-NIDDM Trial,
treatment of people with IGT with the drug
acarbose reduced the risk of developing
diabetes by 25% over 3 years.
Medications

Other medication studies are ongoing. In
addition to preventing progression from
IGT to diabetes, both lifestyle changes and
medication have also been shown to
increase the probability of reverting from
IGT to normal glucose tolerance.
Medications

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